Department of Pathology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, PR China.
Department of Pathology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, PR China.
Cancer Med. 2023 Jul;12(13):14851-14864. doi: 10.1002/cam4.6077. Epub 2023 Jun 7.
Although papillary renal cell carcinoma (PRCC) has a relatively favorable prognosis, a small number of patients with lymph node or distant metastasis have a poor prognosis. Owing to the complex typing and heterogeneity of PRCC, it remains difficult to provide risk stratification. The objective of our research was to identify potential markers of PRCC prognosis.
We performed proteomics and bioinformatics analyses on six pairs of formalin-fixed paraffin-embedded tumor and paired normal tissue samples. The Cancer Genome Atlas (TCGA) data were used to analyze the prognostic value of differentially expressed proteins (DEPs) in PRCC. We verified the expression of the major biomarker through immunohistochemistry (IHC) in 91 PRCC tumor specimens.
Proteomic analysis revealed 1544 DEPs between tumor and paired normal tissues. PRCC transcriptomic data from the TCGA database revealed that compared to non-tumor tissues, the expression of high-mobility group protein A2 (HMGA2) was upregulated in tumor tissues, and patients with high HMGA2 expression exhibited shorter overall survival times. HMGA2 was associated with PRCC tissue subtype and higher cell pleomorphism. Both TCGA and IHC results showed that HMGA2 expression was associated with lymph node metastasis and clinical stage.
HMGA2 was positively correlated with malignant progression and could be a valuable novel prognostic biomarker for PRCC risk stratification.
尽管乳头状肾细胞癌(PRCC)的预后相对较好,但仍有少数发生淋巴结或远处转移的患者预后较差。由于 PRCC 的分型复杂且具有异质性,因此仍然难以进行风险分层。本研究旨在确定 PRCC 预后的潜在标志物。
我们对 6 对福尔马林固定石蜡包埋的肿瘤和配对的正常组织样本进行了蛋白质组学和生物信息学分析。利用癌症基因组图谱(TCGA)数据分析 PRCC 中差异表达蛋白(DEPs)的预后价值。我们通过免疫组织化学(IHC)在 91 例 PRCC 肿瘤标本中验证了主要生物标志物的表达。
蛋白质组学分析显示肿瘤与配对正常组织之间有 1544 个 DEPs。TCGA 数据库的 PRCC 转录组数据分析显示,与非肿瘤组织相比,高迁移率族蛋白 A2(HMGA2)在肿瘤组织中的表达上调,且 HMGA2 高表达的患者总生存时间更短。HMGA2 与 PRCC 组织亚型和更高的细胞多形性相关。TCGA 和 IHC 结果均表明,HMGA2 的表达与淋巴结转移和临床分期相关。
HMGA2 与恶性进展呈正相关,可能是 PRCC 风险分层的有价值的新型预后生物标志物。